Copaescu Ana M, Mouhtouris Effie, James Fiona, Goh Michelle S Y, Phillips Elizabeth J, Trubiano Jason A
Centre for Antibiotic Allergy and Research, Department of Infectious Diseases, Austin Health, Heidelberg, Victoria, Australia.
Department of Infectious Diseases, University of Melbourne, at the Peter Doherty Institute for Infection and Immunity, Victoria, Australia.
World Allergy Organ J. 2024 Dec 7;17(12):101002. doi: 10.1016/j.waojou.2024.101002. eCollection 2024 Dec.
In an exploratory study to assess the potential to individualize T-cell diagnostics in antibiotic-associated severe T-cell mediated hypersensitivity, we focused on drug reaction with eosinophilia and systemic symptoms (DRESS) and the related cytokine outputs IL-4 and IL-5.
Patients with well-phenotyped RegiSCAR ≥4 DRESS, positive intradermal skin testing, and a previous negative IFN-γ Enzyme-Linked ImmunoSpot (ELISpot) assay were prospectively recruited. We specifically performed an ELISpot assay with IL-4 and IL-5 cytokine outputs. As comparative controls, these cytokine outputs were performed simultaneously in patients with a positive IFN-γ release ELISpot result.
Four antibiotic-associated DRESS cases were included. The IL-4 and IL-5 output ELISpot assay demonstrated various results among these patients, with at least 1 cytokine present in all the cases. As for the 2 controls with known positive IFN-γ release, compared to the IFN-γ secretion, the cytokine output using IL-4 and IL-5 showed an increased positivity.
In patients where the early response has suggested a TH2 response such as DRESS, IL-4 and IL-5 cytokine outputs could present an investigational advantage, including when IFN-γ is negative. In the future, larger prospective studies are required to understand the role of varied cytokine outputs in T-cell-mediated hypersensitivities.
在一项探索性研究中,为评估在抗生素相关严重T细胞介导的超敏反应中实现T细胞诊断个体化的潜力,我们聚焦于伴有嗜酸性粒细胞增多和全身症状的药物反应(DRESS)以及相关的细胞因子IL-4和IL-5的产生情况。
前瞻性招募了符合RegiSCAR标准且表现典型、DRESS评分≥4、皮内皮肤试验阳性且之前IFN-γ酶联免疫斑点试验(ELISpot)结果为阴性的患者。我们专门进行了检测IL-4和IL-5细胞因子产生情况的ELISpot试验。作为对照,在IFN-γ释放ELISpot结果为阳性的患者中同时进行这些细胞因子产生情况的检测。
纳入了4例抗生素相关的DRESS病例。IL-4和IL-5产生情况的ELISpot试验在这些患者中显示出不同结果,所有病例中至少存在1种细胞因子。至于2例已知IFN-γ释放阳性的对照,与IFN-γ分泌情况相比,使用IL-4和IL-5检测细胞因子产生情况的阳性率更高。
在早期反应提示为TH2反应的患者(如DRESS患者)中,IL-4和IL-5细胞因子产生情况可能具有研究优势,包括在IFN-γ为阴性时。未来,需要开展更大规模的前瞻性研究以了解不同细胞因子产生情况在T细胞介导的超敏反应中的作用。